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1. Differential expression of prostaglandin E-2 and interleukin-6 in
occlusive and aneurysmal aortic disease
Reilly JM, Miralles K, Wester WN, Sicard GA
SURGERY
126: (4) 624-627 OCT 1999
Abstract:
Background. Both aortoiliac occlusive disease (AIOD) and abdominal
aortic aneurysm disease (AAA) are traditionally considered
degenerative conditions that are caused by athersclerosis. Although it
is becoming apparent that the pathophysiology of each condition has
its own determinants, inflammation is thought to play a role in each.
The purpose of this study was to analyze the inflammatory cytokines
interleukin-6 (IL-6) and prostaglandin E-2 (PGE2) in aortic disease
and compare AAA with AIOD, as well as to compare both with normal
aorta.
Methods. Aortic tissue was harvested at the time of aortic
reconstructive surgery for AAA (n = 13) and AIOD (n = 14) or at time
of organ harvest for normal (n = 16) aortic specimens. Whole organ
cultures were immediately established, and the culture medium was
collected after 72 hours. An enzyme-linked immunosorbent assay was
used to assay for PCE2 and a lymphoproliferative assay was used to
quantitate IL-6. Statistical analysis was performed using paired
2-tail t tests.
Results. Normal aorta expressed much less PGE2 (384 +/- 67 ng/mL) than
either AAA (11, 093 +/- 7, 411 ng/mL) (P <.001) or AIOD (13,719 +/-
3,355 ng/mL) (P <.002). However, there was no statistically
significant difference in PGE2 expression between the AAA and AIOD
groups (P =.44). The IL-6 assay also showed that normal aorta had very
little expression (1,861 +/- 334 U/mL) compared with either AAA
(14,329 +/- 4,159 U/mL) (P =.02) or AIOD (39,805 +/- 8,426) (P <.001).
Comparison between AAA and AIOD revealed significantly higher
expression of IL-6 by the AIOD cultures (P =.03).
Conclusions. AAA and AIOD are associated with increased expression of
the proinflammatory cytokines PGE2 and IL-6. However AIOD is
associated with a much higher level of IL-6 expression than is AAA,
although the level of PGE2 ex;expression is the same. This
differential expression of IL-6 may hell, explain the pathogenesis of
these 2 distinct aortic diseases.
Comment by mdt: This paper by Reilly et al serves as an introduction to the
following offering from the Charing Cross group.
2. Inhibition of prostaglandin E-2 synthesis in abdominal aortic
aneurysms - Implications for smooth muscle cell viability,
inflammatory processes, and the expansion of abdominal aortic
aneurysms
Walton LJ, Franklin IJ, Bayston T, Brown LC, Greenhalgh RM, Taylor GW,
Powell JT
CIRCULATION
100: (1) 48-54 JUL 6 1999
Abstract:
Background-There is no treatment proven to limit the growth of
abdominal aortic aneurysms, in which the histological hallmarks
include inflammation and medial atrophy, with apoptosis of smooth
muscle cells and destruction of elastin.
Methods and Results-Aneurysm biopsies were used for explant cultures,
the preparation of smooth muscle cell cultures, and isolation of
macrophages. Tissue macrophages stained strongly for cyclooxygenase 2.
Prostaglandin E-2 (PGE(2)) concentrations in aneurysm tissue
homogenates, conditioned medium from explants, and isolated
macrophages were 49 +/- 22 ng/g, 319 +/- 38 ng/mL, and 22 +/- 21
ng/mL, respectively. PGE(2) inhibited DNA synthesis and proliferation
in normal aortic smooth muscle cells (IC50, 23.2 +/- 3.8 and 23.6 +/-
4.5 ng/mL, respectively). In smooth muscle cells derived from
aneurysmal aorta, PGE(2) also caused cell death, with generation of
oligonucleosomes. Conditioned medium from the mixed smooth muscle and
monocyte cultures derived from explants also had potent
growth-inhibitory effects, and fractionation of this medium showed
that the growth-inhibitory molecule(s) coeluted with PGE(2). In
explants, indomethacin 10 mu mol/L or mefenamic acid 10 mu mol/L
abolished PGE(2) secretion and significantly reduced LL-1 beta and
IL-6 secretion. In a separate case-control study, the expansion of
abdominal aortic aneurysms was compared in 15 patients taking
nonsteroidal anti-inflammatory drugs and 63 control subjects; median
growth rates were 1.5 and 3.2 mm/y, respectively, P = 0.001.
Conclusions The adverse effects of PGE(2) on aortic smooth muscle cell
viability and cytokine secretion in vitro and the apparent effect of
anti-inflammatory drugs to lower aneurysm growth rates suggest that
selective inhibition of PGE(2) synthesis could be an effective
treatment to curtail aneurysm expansion.
Comment by mdt: In fact, in another study (Br J Surg 1999; 86: 707), the Charing
Cross group reports that the median growth rate of 19 patients taking non-
steroidal anti-inflammatory drugs was 1.8 mm/yr; versus 3.2 mm/yr in controls.
This is an impressive finding.
3. Prevalence of abdominal aortic aneurysms in urology patients referred
for ultrasound
Davies AJ, Winter RK, Lewis MH
ANNALS OF THE ROYAL COLLEGE OF SURGEONS OF ENGLAND
81: (4) 235-238 JUL 1999
Abstract:
During a 3-year period, all urology patients over the age of 50 years
referred for ultrasound investigation of the renal tract, underwent
routine examination of the abdominal aorta. A total of 2281 patients
were examined (1798 men and 483 women) and an abdominal aortic
aneurysm was detected in 57 (2.5%). In men over the age of 65 years,
47 aneurysms were detected (4.9%). The mean time taken to scan the
aorta was 43 s. We recommend the routine practice of examining the
abdominal aorta in all men over the age of 60 years referred for
ultrasound examination of the renal tract.
Comment by mdt: Good idea!